The purpose of this proposal is to further our understanding of the actions and control of human relaxin in both genders. Relaxin is a product of the human corpus luteum of pregnancy and human decidua. It is hypothesized that relaxin is one of the regulators of maternal homeostasis. The effect of corpus luteum number and hCG concentrations on circulating relaxin will be determined. We hypothesize that the hyperrelaxinemia seen in multiple pregnancies and after some superovulation protocols is a cause of premature cervical ripening and premature labor. This hypothesis will be tested in triplet pregnancies and pregnancies resulting from superovulation. Determination of a relationship between prematurity and hyperrelaxinemia may provide new insights into the control and prevention of prematurity. Relaxin may help prepare the pregnant women for parturition and nursing. Proposed studies will determine the effects of relaxin on maternal growth hormone and prolactin secretion. Relaxin is present in human milk. The source and stimuli of milk relaxin secretion will be determined. The effect of potential stimulators and inhibitors of decidual relaxin secretion will be determined in vitro. The control of relaxin secretion will be studied in hCG stimulated human luteinized granulosa cells. Relaxin is produced by the prostate gland, is present in seminal plasma and stimulates sperm motility. The mechanism of action of relaxin on sperm will be determined by studying relaxin receptors and the effect of relaxin on intracellular calcium and pH. The efficacy of relaxin in improving pregnancy rate when added to insemination media for intrauterine insemination will be determined. We hypothesize that this addition of relaxin will increase pregnancy rate and provide a new physiologic therapy for male infertility. These proposed physiological and clinical studies will increase our understanding of the control of pituitary hormone secretion during pregnancy, the role of relaxin in normal pregnancy, the control of relaxin production, the pathological effects of its hypersecretion, the mechanism of its action and its potential usefulness in the therapy of male infertility.